Apparatus and methods for assisted breathing by transvascular nerve stimulation

ABSTRACT

A catheter may include electrodes for transvascular nerve stimulation. The electrodes may be positioned within lumens of the catheter and aligned with apertures in the outer wall of the catheter. The electrodes may produce focused electrical fields for stimulation of one or more nerves. In one embodiment, the catheter may include a set of proximal electrodes and a set of distal electrodes, and the proximal electrodes may stimulate a patient&#39;s left phrenic nerve and the distal electrodes may stimulate a patient&#39;s right phrenic nerve.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit under 35 U.S.C. §119(e) of U.S.Provisional Patent Application No. 61/907,993, filed Nov. 22, 2013, andtitled “Apparatus for Assisted Breathing by Transvascular NerveStimulation and Related Methods.” The entire disclosure of the '993provisional application is incorporated by reference herein.

TECHNICAL FIELD

Embodiments of this disclosure relate to medical apparatus andparticularly to apparatus applicable for the restoration, enhancement,or modulation of diminished neurophysiological functions. Specificembodiments provide apparatus for stimulating the diaphragm muscle toassist breathing by transvascular electrical stimulation of nerves.

BACKGROUND

Electrical stimulation of nerves is widely applied in the treatment of arange of conditions and may be applied to control muscle activity or togenerate sensations. Nerves may be stimulated by placing electrodes in,around, or near the nerves and activating the electrodes by means of animplanted or external source of electricity.

The phrenic nerves normally transmit signals from the brain that causethe contractions of the diaphragm necessary for breathing. However,various conditions can prevent appropriate signals from being deliveredto the phrenic nerves. These include:

-   -   permanent or temporary injury or disease affecting the spinal        cord or brain stem;    -   Amyotrophic Lateral Sclerosis (ALS);    -   decreased day or night ventilatory drive (e.g. central sleep        apnea, Ondine's curse); and    -   decreased ventilatory drive while under the influence of        anesthetic agents and/or mechanical ventilation.        These conditions affect a significant number of people.

Intubation and positive pressure mechanical ventilation (MV) may be usedfor periods of several hours or several days, sometimes weeks, to helpcritically ill patients breathe while in intensive care units (ICU).Some patients may be unable to regain voluntary breathing and thusrequire prolonged or permanent mechanical ventilation. Althoughmechanical ventilation can be initially lifesaving, it has a range ofsignificant problems and/or side effects. Mechanical ventilation:

-   -   often causes ventilator-induced lung injury (VILI) and alveolar        damage which can lead to accumulation of fluid in the lungs and        increased susceptibility to infection (ventilator-associated        pneumonia; VAP);    -   commonly requires sedation to reduce discomfort and anxiety in        acutely intubated patients;    -   causes rapid atrophy of the disused diaphragm muscle        (ventilator-induced diaphragm dysfunction, VIDD);    -   can adversely affect venous return because the lungs are        pressurized and the diaphragm is inactive;    -   interferes with eating and speaking;    -   requires apparatus that is not readily portable; and    -   increases the risk of dying if the patient fails to regain        normal breathing and becomes ventilator-dependent.

A patient who is sedated and connected to a mechanical ventilator cannotbreathe normally because the central neural drive to the diaphragm andaccessory respiratory muscles is suppressed. Inactivity leads to muscledisuse atrophy and an overall decline in well-being. Diaphragm muscleatrophy occurs rapidly and can be a serious problem to the patient.According to a published study in organ donor patients (Levine et al.,New England Journal of Medicine, 358: 1327-1335, 2008) after only 18 to69 hours of mechanical ventilation, all diaphragm muscle fibers hadshrunk on average by 52-57%. Muscle fiber atrophy results in muscleweakness and increased fatigability. Therefore, ventilator-induceddiaphragm atrophy could cause a patient to become ventilator-dependent.It has been reported that over 840,000 ICU patients in the UnitedStates, Europe and Canada become ventilator dependent every year.

There remains a need for cost-effective, practical, surgically simpleand minimally invasive apparatus and methods that may be applied tostimulate breathing. There is also a need for apparatus and methods forfacilitating patients on MV to regain the capacity to breathe naturallyand to be weaned from MV.

SUMMARY

Embodiments of the present disclosure relate to, among other things,medical apparatus and methods for nerve stimulation. Specificembodiments provide apparatus for stimulating breathing by transvascularelectrical stimulation of nerves. Each of the embodiments disclosedherein may include one or more of the features described in connectionwith any of the other disclosed embodiments.

In one embodiment, a catheter may include an elongated tubular memberincluding a first aperture and a second aperture each in an exteriorwall of the elongated tubular member; a first electrode located withinthe elongated tubular member and positioned relative to the firstaperture so that electrical energy associated with the first electrodetravels to or from the exterior of the elongated tubular member throughthe first aperture; and a second electrode located within the elongatedtubular member and positioned relative to the second aperture so thatelectrical energy associated with the second electrode travels to orfrom the exterior of the elongated tubular member through the secondaperture.

The catheter may additionally or alternatively include one or more ofthe following features: a plane that is perpendicular to thelongitudinal axis of the catheter may pass through both the first andsecond apertures; a plane that is perpendicular to the longitudinal axisof the catheter and that passes through the first aperture does not passthrough the second aperture; a line parallel to the longitudinal axis ofthe catheter may pass through both the first and second apertures; thecatheter may further include a third aperture and a fourth aperture eachin the exterior wall of the elongated tubular member located proximateto a distal end of the catheter, and the first and second apertures maybe located proximal to the third and fourth apertures, a third electrodelocated within the elongated tubular member and positioned relative tothe third aperture so that electrical energy associated with the thirdelectrode travels to or from the exterior of the elongated tubularmember through the third aperture, and a fourth electrode located withinthe elongated tubular member and positioned relative to the fourthaperture so that electrical energy associated with the fourth electrodetravels to or from the exterior of the elongated tubular member throughthe fourth aperture; a plane crossing a longitudinal axis of thecatheter may pass through both the first and second electrodes to definea cross-sectional area of the catheter, and the cross-sectional areadoes not include any other electrodes; the first and second electrodesmay be bipolar electrodes configured to stimulate a nerve; the first andsecond apertures and the first and second electrodes may be arrangedsuch that activation of the first and second electrodes creates anelectrical field extending radially outwards from only a portion of acircumference of the catheter; and the catheter may further include afirst electrode assembly extending through a first lumen of the catheterand a second electrode assembly extending through a second lumen of thecatheter, and the first electrode assembly may include the firstelectrode and the second electrode assembly may include the secondelectrode.

In another embodiment, a catheter may include an elongated tubularmember including a first plurality of apertures in an exterior wall ofthe elongated tubular member and a second plurality of apertures in theexterior wall, wherein the second plurality of apertures may be locateddistal to the first plurality of apertures such that a longitudinaldistance between a most distal aperture of the first plurality ofapertures and a most proximal aperture of the second plurality ofapertures is greater than a longitudinal distance between adjacentapertures of the first plurality of apertures and a longitudinaldistance between adjacent apertures of the second plurality ofapertures; a plurality of proximal electrodes located within theelongated tubular member, wherein each of the plurality of proximalelectrodes may be positioned radially inward of a corresponding one ofthe first plurality of apertures; and a plurality of distal electrodeslocated within the elongated tubular member, wherein each of theplurality of distal electrodes may be positioned radially inward of acorresponding one of the second plurality of apertures.

The catheter may additionally or alternatively include one or more ofthe following features: the first plurality of apertures may include atleast three apertures, and the second plurality of apertures may includeat least three apertures; the first plurality of apertures may bearranged in two rows extending in a proximal-distal direction along thecatheter; the second plurality of apertures may be arranged in two rowsextending in a proximal-distal direction along the catheter, and linesparallel to a longitudinal axis of the catheter and passing through thetwo rows of the second plurality of apertures do not pass through thetwo rows of the first plurality of apertures; the first plurality ofapertures may include pairs of apertures, and each pair of apertures maybe arranged such that a plane passing through the centers of the pair ofapertures forms an acute angle with respect to a plane passingperpendicular to a longitudinal axis of the catheter; the firstplurality of apertures may include pairs of apertures, and each pair ofapertures may be arranged such that a plane passing through the centersof the two apertures is perpendicular to a longitudinal axis of thecatheter; a pair of the plurality of proximal electrodes may includebipolar electrodes configured to stimulate a first nerve, and a pair ofthe plurality of distal electrodes includes bipolar electrodesconfigured to stimulate a second nerve; bipolar electrode pairs of theplurality of proximal electrodes may be configured to be selectivelyactivated to create an electrical field extending radially outwards fromonly a portion of a circumference of a longitudinal section of thecatheter that includes the proximal electrodes, and bipolar electrodepairs of the plurality of distal electrodes may be configured to beselectively activated to create an electrical field extending radiallyoutwards from only a portion of the circumference of a longitudinalsection of the catheter that includes the distal electrodes; thecatheter may further include a first electrode assembly and a secondelectrode assembly; each of the first and second electrode assembliesmay include half of the plurality of proximal electrodes; the cathetermay further include a third electrode assembly and a fourth electrodeassembly; each of the third and fourth electrode assemblies may includehalf of the plurality of distal electrodes; the catheter may include afirst lumen, a second lumen, a third lumen, and a fourth lumen; thefirst electrode assembly may be located within the first lumen, thesecond electrode assembly may be located within the second lumen, thethird electrode assembly may be located within the third lumen, and thefourth electrode assembly may be located within the fourth lumen; andeach of the proximal and distal electrodes may be electrically coupledto a distal end of an elongated conductive member.

In yet another embodiment, a catheter may include an elongated member; aproximal set of electrodes positioned along a first longitudinal portionof the elongated member to at least one of emit or receive electricalenergy to or from an exterior of the elongated member along only aportion of a circumference of the first longitudinal portion; and adistal set of electrodes positioned along a second longitudinal portionof the elongated member to at least one of emit or receive electricalenergy to or from an exterior of the elongated member along only aportion of a circumference of the second longitudinal portion. Theproximal and distal sets of electrodes may be positioned such that theproximal set of electrodes is configured to stimulate a patient's leftphrenic nerve and the distal set of electrodes is configured tostimulate the patient's right phrenic nerve.

The catheter may additionally or alternatively include one or more ofthe following features: each of the proximal and distal electrodes mayinclude a conductive tubular member; each of the proximal and distalelectrodes may include an arcuate member having an inner wall and anouter wall; each of the proximal and distal electrodes may beelectrically coupled to an elongated conductive member that extendsproximally from the electrode; the proximal and distal electrodes may beelectrically coupled to the distal ends of the elongated conductivemembers; at least one of the proximal and distal electrodes may includeconductive ink printed on an exterior of the elongated member; theelongated member of the catheter may include a first lumen, a secondlumen, a third lumen, and a fourth lumen; a first plurality of theproximal set of electrodes may be supported by a first elongated tubularmember within the first lumen; a second plurality of the proximal set ofelectrodes may be supported by a second elongated tubular member withinthe second lumen; a first plurality of the distal set of electrodes maybe supported by a third elongated tubular member within the third lumen;and a second plurality of the distal set of electrodes may be supportedby a fourth elongated tubular member within the fourth lumen; at leastone of the proximal and distal electrodes may include a conductivemember fixed to an exterior of the elongated member; the catheter mayfurther include a steering mechanism adapted to deflect a distal end ofthe elongated member; the catheter may further include a ribbon cablehaving a plurality of elongated conductive members; and a proximalportion of the catheter may include a first cross-sectional shape, and adistal portion of the catheter may include a second cross-sectionalshape different than the first cross-sectional shape.

Further aspects of the disclosures and features of example embodimentsare illustrated in the appended drawings and/or described in the text ofthis specification and/or described in the accompanying claims. It maybe understood that both the foregoing general description and thefollowing detailed description are exemplary and explanatory only andare not restrictive of the invention, as claimed.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings, which are incorporated in and constitute apart of this specification, illustrate non-limiting exemplaryembodiments of the present disclosure and together with the descriptionserve to explain the principles of the disclosure.

FIGS. 1A, 1B, and 1C illustrate various views of a catheter havingwindows that may align with nerve-stimulating electrodes within thecatheter, according to an exemplary embodiment.

FIG. 2 is a cross-sectional view of the catheter shown in FIG. 1,showing lumen locations that may receive nerve-stimulating electrodes,according to an exemplary embodiment.

FIG. 3A illustrates an electrode assembly that may be applied forstimulating a left phrenic nerve; FIG. 3B illustrates a cross-sectionalview of an electrode shown in FIG. 3A; FIG. 3C illustrates an electrodeassembly that may be applied for stimulating a right phrenic nerve; andFIG. 3D illustrates a cross-sectional view of an electrode shown in FIG.3C, according to exemplary embodiments.

FIG. 4A illustrates a catheter; FIG. 4B illustrates an electrodeassembly that may be positioned in the proximal end of the catheter ofFIG. 4A and may be applied for stimulating a left phrenic nerve; FIG. 4Cillustrates an electrode assembly that may be positioned in the distalend of the catheter of FIG. 4A and may be applied for stimulating aright phrenic nerve; and FIG. 4D illustrates a cross-sectional view ofthe catheter of FIG. 4A, with the electrode assemblies of FIGS. 4B and4C shown within the lumens of the catheter, according to exemplaryembodiments.

FIG. 5 illustrates the anatomy of selected nerves and blood vessels in aperson's neck and upper torso.

FIG. 6A illustrates electrical field lines produced by a catheter andelectrode pair, according to an exemplary embodiment. FIG. 6Billustrates the electrical field lines of an exemplary prior artelectrode.

FIG. 7A illustrates a catheter having leads sewn into the cathetershaft; FIG. 7B illustrates an electrode assembly that may be insertedinto the catheter of FIG. 7A; FIG. 7C illustrates a partial longitudinalcross section of a distal electrode of FIG. 7A; and FIG. 7D illustratesa transverse cross-sectional view of a proximal electrode pair of FIG.7A showing the inner lumens of the catheter, according to exemplaryembodiments.

FIG. 8A illustrates a catheter having electrodes that are printeddirectly onto the exterior of the catheter; FIG. 8B illustrates anexploded view of distal electrodes of the catheter of FIG. 8A; FIG. 8Cillustrates an exploded view of proximal electrodes of the catheter ofFIG. 8A; and FIG. 8D illustrates a transverse cross-sectional view of anelectrode pair of FIG. 8A, according to exemplary embodiments.

FIG. 9A illustrates a catheter; FIG. 9B illustrates proximal and distalelectrode assemblies that may be inserted into lumens of the catheter ofFIG. 9A; FIG. 9C illustrates an exploded view of the distal electrodeassemblies shown in FIG. 9B; FIG. 9D illustrates an exploded view of theproximal electrode assemblies shown in FIG. 9B; and FIG. 9E illustratesa transverse cross-sectional view of the catheter of FIG. 9A, accordingto exemplary embodiments.

FIGS. 10A and 10B illustrate views of a catheter having electrodes thatare adhered directly onto the exterior of the catheter; FIG. 10Cillustrates an exploded view of electrodes shown in FIG. 10A; FIG. 10Dillustrates a transverse, cross-sectional view of a single electrode;and FIG. 10E illustrates a transverse, cross-sectional view of anelectrode pair of FIG. 10A, according to exemplary embodiments.

FIG. 11A illustrates a catheter; FIG. 11B illustrates proximal anddistal electrode assemblies held together by injection molding,according to a first exemplary embodiment; FIG. 11C illustrates anexploded view of the distal electrodes shown in FIG. 11B; FIG. 11Dillustrates electrode assemblies held together by injection molding,according to a second exemplary embodiment; FIG. 11E illustrates anexploded view of the distal electrodes shown in FIG. 11D; and FIG. 11Fillustrates a transverse, cross-sectional view of the catheter of FIG.11A, showing the catheter lumens and electrode assemblies of FIG. 11Bwithin the lumens.

FIG. 12A illustrates a catheter; FIG. 12B illustrates a perspective viewof a distal electrode assembly; FIG. 12C illustrates a perspective viewof a proximal electrode assembly; FIG. 12D illustrates a side view ofthe distal electrode assembly of FIG. 12B; FIG. 12E illustrates a sideview of the proximal electrode assembly of FIG. 12C; FIG. 12Fillustrates a transverse cross-sectional view of a distal electrode ofFIG. 12D; FIG. 12G illustrates a transverse cross-sectional view of aproximal electrode of FIG. 12E; 12H illustrates a transversecross-sectional view of the catheter of FIG. 12A with two distalelectrode assemblies of FIG. 12B within the catheter lumens; FIG. 12Iillustrates a transverse cross-sectional view of the catheter of FIG.12A with two proximal electrode assemblies of FIG. 12C within thecatheter lumens; FIG. 12J illustrates the view of FIG. 12H with ECGwires through a central lumen of the catheter; and FIG. 12K illustratesthe view of FIG. 12I with ECG wires through a central lumen, accordingto exemplary embodiments.

FIG. 13A illustrates a catheter; FIG. 13B illustrates a perspective viewof a distal electrode assembly having arcuate electrodes; FIG. 13Cillustrates a perspective view of a proximal electrode assembly havingarcuate electrodes; FIG. 13D illustrates a side view of the distalelectrode assembly of FIG. 13B; FIG. 13E illustrates a side view of theproximal electrode assembly of FIG. 13C; FIG. 13F illustrates atransverse cross-sectional view of a distal electrode of FIG. 13D; FIG.13G illustrates a transverse cross-sectional view of a proximalelectrode of FIG. 13E; 13H illustrates a transverse cross-sectional viewof the catheter of FIG. 13A with two distal electrode assemblies of FIG.13B within the catheter lumens; FIG. 13I illustrates a transversecross-sectional view of the catheter of FIG. 13A with two proximalelectrode assemblies of FIG. 13C within the catheter lumens; FIG. 13Jillustrates the view of FIG. 13H with ECG wires through a central lumenof the catheter; and FIG. 13K illustrates the view of FIG. 13I with ECGwires through a central lumen, according to exemplary embodiments.

FIG. 14 illustrates individually shielded ECG wires, according to anexemplary embodiment.

FIGS. 15A, 15B, and 15C illustrate various views of a steering mechanismfor steering a distal catheter tip, according to an exemplaryembodiment.

FIG. 16A illustrates a catheter having a steering mechanism thatincludes a stiffening element and two pull wires that are adhered withina central lumen of the catheter; FIG. 16B illustrates a transversecross-section of the catheter of FIG. 16A showing the steering mechanismin a central lumen; FIG. 16C illustrates a side view of the steeringmechanism; FIG. 16D illustrates a longitudinal cross-sectional view ofthe distal portion of the catheter of FIG. 16A showing an exploded viewof the steering mechanism; and FIG. 16E illustrates an exploded view ofa portion of the steering mechanism shown in FIG. 16D, according toexemplary embodiments.

FIGS. 17A and 17B illustrate a steering mechanism that includes twohypodermic tubes with laser cut portions to help direct bending,according to an exemplary embodiment.

FIG. 18A illustrates a catheter having a steering mechanism thatincludes diametric lumens, each with a pull wire; FIG. 18B illustratesthe pull wires of the steering mechanism; FIG. 18C illustrates atransverse cross-sectional view of the catheter of FIG. 18A; FIG. 18Dillustrates a longitudinal cross-sectional view of the distal portion ofthe catheter of FIG. 18A showing the steering mechanism; and FIG. 18Eillustrates an exploded view of a portion of the steering mechanismshown in FIG. 18D, according to exemplary embodiments.

FIG. 19A illustrates a catheter having a steering mechanism thatincludes a single push/pull wire inserted through a hypodermictube/compression coil and adhered within a central lumen; FIG. 19Billustrates the steering mechanism; FIG. 19C illustrates a transversecross-sectional view of the catheter of FIG. 19A; FIG. 19D illustrates alongitudinal cross-sectional view of the distal portion of the catheterof FIG. 19A showing the steering mechanism; and FIG. 19E illustrates anexploded view of a portion of the steering mechanism shown in FIG. 19D,according to exemplary embodiments.

FIGS. 20A, 20B, and 20C illustrate catheters having different windowalignments, according to exemplary embodiments.

FIG. 21 illustrates a dorsal view of human blood vessels and left andright phrenic nerves, with a pre-shaped catheter inserted within theblood vessels, according to an exemplary embodiment.

FIG. 22A illustrates a catheter having longitudinal slots along itslength; and FIG. 22B illustrates a cross-sectional view of the catheterof FIG. 22A, according to an exemplary embodiment.

FIG. 23A illustrates a catheter having longitudinal slots along aportion of its length; and FIG. 23B illustrates a cross-sectional viewof the catheter of FIG. 23A, according to an exemplary embodiment.

FIG. 24A illustrates electrode assemblies within the catheter of eitherFIG. 22A-22B or 23A-23B, with a sleeve shown covering a portion of thecatheter; and FIG. 24B illustrates a cross-sectional view of FIG. 24A,according to an exemplary embodiment.

FIG. 25A illustrates a side view of a ribbon wire catheter with an innercatheter core and an outer insulation jacket; FIG. 25B illustrates aperspective view of the catheter of FIG. 25A; and FIG. 25C illustrates across-sectional view of the catheter of FIG. 25A, according to anexemplary embodiment.

FIG. 26A illustrates electrodes attached to a ribbon wire catheter; FIG.26B illustrates a cross-sectional view of a proximal electrode pair ofthe catheter of FIG. 26A; FIG. 26C illustrates a cross-sectional view ofa distal electrode pair of the catheter of FIG. 26A; FIG. 26Dillustrates the ribbon wire catheter of FIG. 26A, shown attached to aguidewire lumen and in a closed position; FIG. 26E illustrates theribbon wire catheter of FIG. 26D in an open position; FIG. 26Fillustrates the ribbon wire catheter of FIG. 26D in relation to a vesselwall and target nerve; FIG. 26G illustrates a perspective view of theribbon wire catheter of FIG. 26A in an open position; and FIG. 26Hillustrates the ribbon wire catheter of FIG. 26G with a pull wire,according to exemplary embodiments.

DETAILED DESCRIPTION

Throughout the following description, specific details are set forth toprovide a more thorough understanding to persons skilled in the art. Thefollowing description of examples of the technology is not intended tobe exhaustive or to limit the system to the precise forms of any exampleembodiment. Accordingly, the description and drawings are to be regardedin an illustrative, rather than a restrictive, sense.

General Overview

In general, embodiments of this disclosure relate to medical devices andmethods for electrically stimulating a patient's nerves. In oneembodiment, the patient's nerves may be stimulated to activate thediaphragm to restore or control breathing.

The medical devices described herein may include several components,including a catheter having an elongated tubular member and one or moreelectrode assemblies, a signal generator to provide stimulation energyto the electrode assemblies, and one or more sensors to sense thecondition of the patient and adjust the stimulation signals. The medicaldevices may further include a steering mechanism. Various embodiments ofcatheters are disclosed, including windowed catheters, multi-lumencatheters, and ribbon catheters. In addition, various embodiments ofelectrode assemblies are disclosed, which may be used alone, incombination with other electrode assemblies, and with any of thedisclosed elongated tubular members that form the outer portion of thecatheters. The term “catheter” may used herein to refer to the elongatedtubular member of the catheter or to the assembled catheter as a whole,which may include electrode assemblies, a steering mechanism, and anyother components within or coupled to the elongated tubular member.Several types of steering mechanisms are also described.

The different embodiments of the various medical device components(e.g., catheters, electrode assemblies, steering mechanisms, etc.) maybe combined and used together in any logical arrangement. Furthermore,individual features or elements of any described embodiment may becombined with or used in connection with the individual features orelements of other embodiments. The various embodiments may further beused in different contexts than those specifically described herein. Forexample, the disclosed electrode structures may be combined or used incombination with various deployment systems known in the art for variousdiagnostic and/or therapeutic applications.

During use, the medical devices (e.g., a catheter with one or moreelectrode assemblies) may be inserted into a patient's blood vesselssuch that the electrode assemblies are near the patient's nerves. Theelectrode assemblies may then be used for transvascular electricalstimulation of the patient's nerves. The disclosed devices may beoptimized for rapid, temporary deployment in a patient and easy removalfrom the patient. The disclosed devices may be used, for example, forrestoring breathing, treating conditions such as disuse muscle atrophyand chronic pain, or for any other procedures involving nervestimulation. The disclosed devices may be used to treat acute or chronicconditions.

Medical Device Overview: Catheter and Electrode Assemblies

Referring to FIGS. 1-6B, an overview of an exemplary embodiment of amedical device and a method of use will be described. Later drawingswill be referenced to describe additional or alternative embodiments ofthe various medical device components.

FIGS. 1A, 1B, and 1C illustrate various views of a catheter 10 accordingto an exemplary embodiment. In FIGS. 1A, 1B, and 1C, the catheter 10 isshown in a different rotational position around a longitudinal axis A-Athrough the catheter 10. The catheter 10 may include an elongatedtubular member made of extruded polyurethane (or any other suitablebiocompatible material). As can be seen in FIG. 1A, the catheter 10 mayinclude a row of distal windows 16, which may be aligned along alongitudinal axis near a distal end 12 of the catheter 10. The catheter10 may further include a second row of distal windows 16, which can bepartially seen in FIG. 1C. At a position on the catheter 10 proximal towindows 16 (in some cases at the proximal end of the catheter 10), thecatheter 10 may similarly include two rows of proximal windows 18. Thesewindows will be referred to herein as “proximal windows 18” todistinguish the proximal set of windows 18 from the distal set ofwindows 16. In other embodiments, the catheter 10 may include three ormore rows of distal windows 16 or three or more rows of proximal windows18. The proximal windows 18 may have the same or different structuralfeatures as the distal windows 16. A section of the catheter 10 betweenthe proximal windows 18 and the distal windows 16 may be free ofwindows.

In one embodiment, the catheter 10 includes six distal windows 16 andtwelve proximal windows 18. However, in other embodiments, the catheter10 may include fewer or more proximal or distal windows. For example, inother embodiments, the catheter 10 may include two, four, eight, ten,twelve, or more distal windows 16, and/or two, four, six, eight, ten, ormore than twelve proximal windows 18. The distal windows 16 and proximalwindows 18 may be configured in pairs such that the catheter 10 has aneven number of distal windows 16 and an even number of proximal windows18. However, the number of windows 16 or 18 may also be an odd number.

The windows 16, 18 may be cut (e.g. by a laser, manual skive, drill,punch, etc.) through the exterior wall of catheter 10, or the windowsmay be formed by any other suitable method, such as during an extrusionprocess or other manufacturing process. The windows 16, 18 may beelongated along the longitudinal axis A-A. They may have a rectangular,oval, square, or any other shape. The windows 16, 18 may be aperturesconfigured to allow electrical signals to travel from an interior lumenof the catheter 10 to the exterior of the catheter 10. In an additionalor alternative embodiment, the windows 16, 18 may be covered by amaterial that allows electrical signals to pass through. As can be seenin the figures, the proximal windows 18 may be rotationally offset fromthe distal windows 16. In other words, in one embodiment, a straightline drawn proximally through a row of distal windows 16 does not passthrough a row of proximal windows 18. In other embodiments, one or morerows of proximal windows 18 may be aligned with a corresponding row ofdistal windows 16.

The dimensions of catheter 10 may be customized in accordance with theanatomy of a particular patient. However, in some embodiments, thelength of the section of the catheter 10 that includes the proximalwindows 18 may be 10 cm or less, between 3-5 cm, or between 1-3 cm. Thedistance between two adjacent proximal windows 18 (whether the windowsare longitudinally adjacent or adjacent on the same row of windows) maybe 5 cm or less, 3 cm or less, or may be around 1 cm. The length of thesection of the catheter 10 that includes the distal windows 16 may be 6cm or less, between 2-4 cm, or between 1-2 cm. The distance between twoadjacent distal windows 16 (whether longitudinally adjacent or adjacenton the same row of windows) may be 5 cm or less, 3 cm or less, or may bearound 1 cm. The length of the section of the catheter between proximalwindows 18 and distal windows 16, which may be free of windows, may be12 cm or less, 10 cm or less, or 8 cm or less. The windows 16, 18 mayhave a length of 6 mm or less, 5 mm or less, 4 mm or less, 3 mm or less,2 mm or less, or 1 mm or less. In one embodiment, the windows may have alength that is less than the length of corresponding electrodes that areelectrically exposed through the windows. It should be understood thatthe above catheter dimensions are exemplary only, and the catheter 10may have dimensions that vary from the above ranges and specificmeasurements.

FIG. 2 illustrates a cross-sectional view along plane II-II (see FIG.1A) of catheter 10. The interior of catheter 10 may include one or morelumens. In one embodiment, the catheter 10 may include six lumens 20,22, 24, 26, 28, 30, although the catheter 10 may include fewer or morelumens. The lumens 20, 22, 24, and 26 may be electrode assembly lumensused to receive electrode assemblies described in further detail below.In one embodiment, proximal windows 18 may create a pathway between theinterior of lumens 20, 22 and the exterior of catheter 10. Thus, lumens20, 22 may receive electrodes that align with the proximal windows 18shown in FIGS. 1A-1C. Similarly, distal windows 16 may create a pathwaybetween the interior of lumens 24, 26 and the exterior of catheter 10,and lumens 24, 26 may receive electrodes that align with the distalwindows 16 shown in FIGS. 1A-1C. Lumens 20, 22 may therefore be proximalelectrode assembly lumens, and lumens 24, 26 may be distal electrodeassembly lumens. As will be described in greater detail below, theproximal electrode assemblies placed in lumens 20, 22 may be used tostimulate a patient's left phrenic nerve, and the distal electrodeassemblies placed in lumens 24, 26 may be used to stimulate a patient'sright phrenic nerve. Lumen 28 may receive a guidewire, and lumen 30 mayreceive a steering mechanism, other instruments, wires, or may be usedto transport fluid to or from a working site.

FIG. 3A illustrates an exemplary embodiment of a proximal electrodeassembly 32, and FIG. 3B illustrates a cross-sectional view of a singleelectrode 36 along plane IIIB-IIIB of FIG. 3A. In one embodiment, theproximal electrode assembly 32 may include six proximal electrodes 36.Similarly, FIG. 3C illustrates an exemplary embodiment of a distalelectrode assembly 34, and FIG. 3D illustrates a cross-sectional view ofa single electrode 38 along plate IIID-IIID of FIG. 3C. The distalelectrode assembly 34 may include three distal electrodes 38. The twoelectrode assemblies 32 and 34 may differ from one another in terms ofnumber of electrodes, structural features of the electrodes, andstructural features of the assembly as a whole.

A proximal electrode assembly 32 may be held within one of proximalelectrode assembly lumens 20, 22 of catheter 10, and a second proximalelectrode assembly 32 may be held within the other of proximal electrodeassembly lumens 20, 22 of catheter 10. Similarly, distal electrodeassembly 34 may be held within one of distal electrode assembly lumens24, 26 of catheter 10, and a second distal electrode assembly 34 may beheld within the other of distal electrode assembly lumens 24, 26 ofcatheter 10. This combination of two proximal electrode assemblies 32and two distal electrode assemblies 34 within the lumens of catheter 10may allow the twelve proximal electrodes 36 to align with the twelveproximal windows 18 and the six distal electrodes 38 to align with thesix distal windows 16.

FIGS. 3A and 3B will be referenced to describe proximal electrodeassembly 32 in greater detail. Individual electrical leads 44 may becoiled together to form cable 40 of the proximal electrode assembly 32.Each lead 44 may include an elongated conductive member 45 and may besurrounded by a layer of non-conductive material 46. In one embodiment,the lead 44 may be a wire, the elongated conductive member 45 mayinclude strands of stainless steel or another conductive material, andthe non-conductive material 46 may be a layer of insulation. The leads44 may deliver electrical or other signals to and from the electrodes36.

In one embodiment, the cable 40 may include seven leads 44. Of theseseven leads 44, six may be individually de-insulated at certainlocations (e.g., underneath electrodes 36, as shown in FIG. 3B) toexpose the conductive member 45 underneath. A conductive connector 42,which may be thin, flexible, and made of stainless steel or anotherconductive material, may be joined (e.g. mechanically, adhesive,micro-welded, etc.) to the exposed conductive member 45 and wrappedtransversely around the cable 40. The conductive connector 42 mayprovide a contact surface between the exposed conductive member 45 andan electrode 36. In one embodiment, the electrode 36 may be aplatinum-10% iridium (or any other suitable implantable electrodematerial like stainless steel, platinum, titanium nitride, coatedstainless steel, etc.) ring electrode, which is crimped (or adhered,microwelded) to the exterior of the conductive connector 42 and cable40. The seventh insulated lead 44 shown in the center of FIG. 3B mayhelp support and stiffen the cable 40. The seventh lead 44 also may beused to carry other types of signals, for example signals from a sensoror ECG signals. In total, as noted above, two seven-lead proximalelectrode assemblies may be inserted into the lumens 20, 22 of catheter10.

Referring to FIGS. 3C and 3D, cable 48 of a distal electrode assembly 34may include three electrical leads 44, which may be constructed in asimilar manner as described in connection with the proximal electrodeassembly 32. Three electrodes 38 may be mounted to conductive connectors42, which are connected to exposed conductive members 45 ofcorresponding leads 44. In additional or alternative embodiments,partial or semi-circular electrodes may be used instead of ringelectrodes 36, 38. The number of lumens within catheter 10, number ofcables 40, 48, the number of electrodes 36, 38 on each cable 40, 48,respectively, and the distance between electrodes 36, 38, along withother structural features, may be varied to fit particular applications.

In one embodiment, any of the proximal electrodes 36 or the distalelectrodes 38 may be used to measure electrical signals or other datafrom within the patient's body. In other words, in addition oralternatively to emitting or receiving electrical energy to produce alocalized current for nerve stimulation, the electrodes may serve assensors that receive electrical or other types of information from thepatient.

FIGS. 4A-4D illustrate how multiple electrode assemblies 32, 34 may bewithin the lumens of catheter 10. A catheter 10 is depicted in FIG. 4A,two proximal electrode assemblies 32 are depicted in FIG. 4B, and twodistal electrode assemblies 34 are depicted in FIG. 4C. The two proximalelectrode assemblies 32 may be placed within lumens 20, 22 of catheter10 such that the electrodes 36 align with proximal windows 18.Similarly, the two distal electrode assemblies 34 may be placed withinlumens 24, 26 of catheter 10 such that the electrodes 38 align withdistal windows 16 (not shown in FIG. 4A). Once aligned, the electrodeassemblies 32, 34 may be fixed (e.g. with adhesive or by any otherstructure or method) within their respective catheter lumens. FIG. 4Dillustrates a cross-section of catheter 10, taken along plane IVD-IVD ofFIG. 4A, that shows the catheter with two proximal electrode assemblies32 and two distal electrode assemblies 34 within lumens 20, 22, 24, 26of catheter 10.

Referring to FIG. 5, a medical device 50 may include a catheter 10having two proximal electrode assemblies 32 and two distal electrodeassemblies 34. The electrode assemblies 32, 34 may be within theelongated tubular member of catheter 10 such that electrodes 36 areexposed through proximal windows 18 and electrodes 38 are exposedthrough distal windows 16. The cables 40, 48 formed of electrical leads44 may exit through the proximal end of the catheter 10 and may beattached (e.g. by solder, crimp, PCB, etc.) to connectors 52, 54.

To assemble medical device 50, the electrode assemblies 32, 34, whichmay include leads 44 and electrodes 36, 38, may be introduced into oneor more lumens through lumen openings at either the proximal end ordistal end of catheter 10. For example, the leads 44 may be insertedinto a proximal end of the catheter 10 and threaded or pulled throughone or more lumens until electrodes 36, 38 are located at predeterminedlocations in a more distal portion of the catheter 10. Portions of thecatheter wall may be removed, either before or after insertion of theelectrode assemblies 32, 34, to create windows 18, 16. Windows 18, 16may expose the electrodes, allowing for a conductive path between theelectrodes 36, 38 and the blood vessel lumen in which the medical device50 may be placed.

Referring still to FIG. 5, in an exemplary method of use, the medicaldevice 50 may be used for transvascular stimulation of nerves in theneck and/or chest of a human or other mammal (e.g., a pig, achimpanzee). FIG. 5 illustrates the anatomy of selected nerves and bloodvessels in the neck and chest of a human and, in particular, therelative locations of the left phrenic nerve (PhN) 56, right phrenicnerve 58, vagus nerves (VN) (not shown), external or internal jugularveins (JV) 60, brachiocephalic veins (BCV) 62, superior vena cava (SVC)64, and left subclavian vein (LSV) 66.

The medical device 50 may be used to rhythmically activate the diaphragmby inserting the catheter 10, with one or more electrode assemblies 32,34, percutaneously into central veins of a patient. Percutaneousinsertion of the catheter 10 may be accomplished by the Seldingertechnique, in which a guide wire is inserted through a hypodermic needleinto a vein. The distal tip of the catheter is then passed over theguide wire and advanced into the vein. The shape and mechanicalproperties of the catheter may be designed to urge the catheter 10 togently hug the vein wall in regions adjacent to the right and leftphrenic nerves, as shown in FIG. 5.

In the embodiment of FIG. 5, the medical device 50 may be inserted intothe left subclavian vein 66 and advanced into the superior vena cava 64.In another configuration, not shown, the medical device 50 may beinserted into the left jugular vein and advanced into the superior venacava 64. The catheter 10 may be inserted in a minimally-invasive way andmay be temporarily placed into, and thus removable from, the patient. Inone embodiment, the windows 18 are oriented such that, when the catheteris inserted into the left subclavian vein 66, the six pairs of windows18 are directed posteriorly towards the left phrenic nerve 56 and thethree pairs of distal windows 16 are directed laterally towards theright phrenic nerve 58.

In one embodiment, the electrode assemblies 34 may include electrodes 38arranged and oriented to most effectively stimulate a nerve extendingparallel to the catheter 10 (e.g., the right phrenic nerve 58 in FIG.5), and the electrode assemblies 32 may include electrodes 36 arrangedand oriented to most effectively stimulate a nerve extending attransverse or right angles to the catheter 10 (e.g., the left phrenicnerve 56 in FIG. 5). In an additional or alternative embodiment, theelectrode assemblies 34 may include electrodes 38 arranged and orientedto most effectively stimulate a nerve extending at transverse or rightangles to the catheter 10, and the electrode assemblies 32 may includeelectrodes arranged and oriented to most effectively stimulate a nerveextending parallel to the catheter 10. In the embodiments describedabove, the electrodes 38 of the electrode assemblies 34 have been placedin a more distal location along catheter 10 than the electrodes 36 ofelectrode assemblies 32. However, in other embodiments, the electrodeassemblies 32 may be arranged within the catheter 10 such that theirelectrodes 36 are more distal than the electrodes 38 of the electrodeassemblies 34. In this alternative embodiment, the windows 16, 18 of thecatheter 10 may be configured to accommodate the alternative placementof the electrode assemblies 32, 34.

Once the catheter is fully inserted into the patient, various pairs ofbipolar electrode combinations can be tested to locate nerves ofinterest and to determine which electrodes most effectively stimulatethe nerves of interest. For example, in one embodiment, testing may bedone to locate the right phrenic nerve 58 and to determine which pair ofelectrodes 38 (out of the distal set of electrodes 38) most effectivelystimulate the right phrenic nerve 58. Similarly, testing may be done tolocate the left phrenic nerve 56 and to determine which pair ofelectrodes 36 (out of the proximal set of electrodes 36) mosteffectively stimulate the left phrenic nerve 56. As a non-limitingexample, testing could involve the use of a signal generator tosystematically send electrical impulses to selected electrodes. Byobserving the patient's condition or by using sensors, the idealelectrode pairs may be identified.

FIG. 6A illustrates a cross-sectional view of catheter 10 along theplane VIA-VIA shown in FIG. 4A and will be referenced to describeselective activation of a pair of electrodes for stimulating a nerve.The electrodes of FIG. 6A may be any electrode pair located at anylocation along catheter 10, and the nerve 56 may be any nerve locatedparallel, transverse, or at any other orientation with respect tocatheter 10. However, for ease of description, proximal electrodes 36and left phrenic nerve 56 are referenced in connection with FIG. 6A,even though left phrenic nerve 56 is shown transverse to catheter 10 inFIG. 5. Although not shown in FIG. 6A, a pair of distal electrodes 38also may be selectively activated to stimulate the right phrenic nerve58.

During “selective activation,” an electrical potential may be createdbetween a pair of selected bipolar electrodes, such as between a firstelectrode 36′ and a second electrode 36″. The first electrode 36′ may bealigned with a first window 18′, and the second electrode 36″ may bealigned with a second window 18″. The arrangement of the first andsecond electrodes 36′, 36″ and the first and second windows 18′, 18″ maycreate an electrical field 68 in the vicinity of first and second.windows 18′, 18″. The first and second electrodes 36′, 36″ may beselected to effectively target a nerve, such as the left phrenic nerve56 shown in FIG. 6A or another nerve near the electrodes 36′, 36″. Thewindows 18′, 18″ and the resulting electrical field 68 may therefore beoriented towards the left phrenic nerve 56 or other target nerve.

During nerve stimulation, electrical current flows from one of theelectrodes 36′, 36″ to the other of the electrodes 36′, 36″, flowingthrough the windows 16′, 16″ and through the blood and surroundingtissues. The catheter 10 with windows 16′, 16″ therefore acts as aninsulative barrier that constrains and focuses the electrical field 68,rather than allowing the electrical field 68 to expand radially outwardsin all directions. The focused electrical field allows target nervestimulation at lower energy levels and avoids stimulating unwantednerves or other structures. In some embodiments, the stimulation currentmay be between 10-6000 nC (nanocoulombs) or between 50-500 nC.

FIG. 6B illustrates an exemplary prior art nerve stimulation device 70that may be used to stimulate a nerve 78. The prior art device 70 mayinclude lead wires 72 and an electrode 74. The device 70 may be insertedinto a blood vessel 76, and an electrical field 80 may be created aroundthe device 70. As can be seen in FIG. 6B, the electrical field 80 may becreated around the circumference of the device 70. Although it maytarget a nerve 78, the electrical field is not confined to a specificlocation and therefore may also target other anatomical structureswithin the patient. Thus, in general, the windows 16, 18 of catheter 10may allow the use of lower and safer electrical currents to activate thephrenic nerves 56, 58 and prevent overstimulation or unwanted activationof nearby structures such as other nerves, muscles, or the heart.

Electrode Assembly Embodiments

FIGS. 7A-13K illustrate additional or alternative embodiments ofelectrodes and electrode assemblies that may be used with any of thecatheters described herein. The below embodiments may be variations ofthe electrode assemblies and electrodes described previously. Therefore,features not mentioned may be unchanged or logical modifications of theabove-described embodiments. For ease of reference, proximal electrodes36, proximal electrode assemblies 32, distal electrodes 38, and distalelectrode assemblies 34 of each embodiment will be referred to using thesame reference numerals as used above, even though some features ofthese components may be modified in the below embodiments.

Bare/Sewn Wires

Referring to FIGS. 7A-7D, the layer of non-conductive material 46 may beremoved from portions of leads 44 to expose the underlying conductivemember 45. FIG. 7A illustrates a catheter 10, and FIG. 7B illustrates aproximal electrode assembly 32. The exposed conductive members 45(straight or coiled for increased surface area) of leads 44 may bepositioned within windows 16 or 18 of the catheter 10 and, in someembodiments, may extend radially out of the windows 16, 18. In anotherembodiment, as shown in FIG. 7C, the conductive member 45 may pass outof a lumen of the catheter 10 through an aperture in the catheter outerwall, travel in a proximal-distal direction, and then pass back throughanother aperture in the outer wall of catheter 10. The portion of theconductive member 45 that forms an electrode 36, 38 may be the distalend of a lead 44. The insulated leads 44 may additionally oralternatively be sewn into the catheter 10, leaving the exposedconductive member 45 on the exterior of the catheter 10 and theremaining insulated lead 44 inside a catheter lumen. FIG. 7D illustratesa cross-section of catheter 10 through a pair of proximal electrodes 36that include exposed conductive members 45.

In some embodiments, a conductive member, such as an electrode describedin connection with FIGS. 10A-10E, may be fixed (e.g., with adhesive,heat fusion, etc.) to the exterior of catheter 10 and in electricalcontact (e.g., mechanically, microwelded) with the exposed conductivemember 45. Fixing such a conductive member to the exposed conductivemember 45 may increase certain electrical properties of the electrode,such as conductivity and surface area, relative to an electrode thatonly includes the exposed conductive member 45. Examples of conductivemember material include platinum, platinum iridium, gold, stainlesssteel, titanium nitride, MP35N, palladium, etc.

Printed Electrodes

FIG. 8A illustrates a catheter having electrodes and leads that areprinted directly onto the exterior of catheter 10. FIG. 8B illustratesan exploded view of distal electrodes 38 of the catheter 10, FIG. 8Cillustrates an exploded view of proximal electrodes 36 of catheter 10,and FIG. 8D illustrates a transverse cross-sectional view of a proximalelectrode pair 36 taken along plane VIIID-VIIID of FIG. 8C. Electrodes36, 38 may be formed by conductive inks (such as silver flakes or carbonflakes suspended in polymer). These conductive inks may be deposited andadhered directly onto the catheter 10 and sealed, except for the exposedelectrodes 36, 38, with an outer polyurethane or other flexibleinsulative film. The exposed electrodes 36, 38 also may be coated (e.g.,with titanium nitride) for purposes such as one or more of: enhancingelectrical properties, such as conductivity and surface area; providingcorrosion resistance; and reducing the potential for formation of silveroxide which could be toxic. As can be seen in FIG. 8C, the conductiveink trace of distal electrodes 38 may travel proximally along catheter10 past the proximal electrodes 36.

The use of printed electrodes may reduce the overall complexity of thedesign while maximizing the useable catheter lumen space, withoutchanging the catheter profile or flexibility too drastically. However,in some embodiments, the profile of the catheter may be reduced becauseof the space saved by using electrodes printed on the exterior of thecatheter. In an additional or alternative embodiment, one or severalcatheter lumens may be used for fluid delivery, blood sampling, orcentral venous pressure monitoring. In another additional or alternativeembodiment, several of the catheter lumens, such as lumens 20, 22, 24,26 may be eliminated since there are no catheter assemblies as describedin connection with other embodiments. Thus, in one embodiment, thecatheter 10 may include only lumen 28 and lumen 30. If the catheter 10with printed electrodes includes fewer than the six lumens shown in FIG.2, for example, its cross-sectional area may be reduced, one or more ofthe fewer lumens may be made larger to accommodate larger tools or otherobjects, or one or more smaller lumens may be added to accommodate toolsor other objects.

Electrode-Supporting Catheters

FIGS. 9A-9E illustrate electrodes 36, 38 supported by catheters 94, 96that may be placed within a lumen of catheter 10. In this embodiment,proximal electrodes 36 may be joined by an electrode catheter 94, anddistal electrodes 38 may be joined by an electrode catheter 96. Thecatheters 94, 96 may be elongated tubular members that include anon-conductive material. The electrodes 36, 38 may be crimped onto thecatheters 94, 96 and may be electrically connected to conductive members45 of leads 44 through the walls of the electrode catheters 94, 96. Thecatheters 94, 96 may have cross-sectional areas that are smaller thanthe cross-sectional areas of their respective lumens of catheter 10 sothat catheters 94, 96 may be inserted into the lumens of catheter 10.When catheters 94, 96 are inserted into catheter 10, the electrodes 36,38 may be aligned with windows 18, 16 of catheter 10 and fixed in place,similar to other embodiments. Although not shown in FIG. 9E, leads 44may travel in a proximal-distal direction through the electrodecatheters 94, 96.

In an additional or alternative embodiment, one or more catheters havinga single electrode 36 or 38, or a pair of bipolar electrodes, may beinserted into a lumen of catheter 10 during a procedure (i.e., whilecatheter 10 is within a patient's vascular system) and advanced tovarious windows 18, 16 until optimal locations are found. By doing so,less material may be used, which may drive down the cost of productionof the medical device 50.

Exterior Electrodes

FIGS. 10A-10E illustrate electrodes 36, 38 on the exterior of a catheter10. In the embodiment of FIGS. 10A-10E, electrodes 36, 38 may beconnected (microwelded, etc.) to a lead 44 and may be fixed (e.g.,crimped, adhered, etc.) onto the exterior of catheter 10. The lead 44may be inserted through the wall of the catheter 10 (e.g., through awindow 16, 18) and into a lumen within the catheter 10.

In other embodiments, one or more ring electrodes may be fixed to theexterior of the catheter 10. To facilitate directional targeting of oneor more nerves, an insulative coating may be applied to cover a portionof the electrodes.

Injection Molding

FIGS. 11A-11F illustrate an embodiment in which the manufacturingprocess of electrode assemblies 32, 34 may include injection molding. Toobtain the electrode configuration shown in FIGS. 11B and 11C,electrodes 36, 38 may be individually attached to leads 44 by injectionmolding, with the electrodes 36, 38 in electrical contact withconductive members 45. The molding process may form a covering 98 aroundeach lead 44. The covering 98 may include a non-conductive material,such as plastic. The electrodes 36, 38 may be flat, semi-circular, orany other suitable shape. Similarly, the covering 98 may form any shapearound the leads 44, such as the shape shown in FIG. 11F.

In another embodiment, shown in FIGS. 11D and 11E, the electrodes 36, 38and bundle of leads 44 may be placed within an injection molding jigthat injects material, such as plastic, around the bundle of leads 44 toanchor the electrodes in place, forming a covering 98 but in oneembodiment leaving at least a portion of the electrodes 38 exposed. Insome embodiments, the electrodes may be covered by a thin layer ofpolymer, which may be removed in a subsequent step. In the embodiment ofFIG. 11C, the covering 98 may be placed in the longitudinal vicinity ofthe electrodes and might only surround a single lead, and thus may bereferred to as “partial.” In the embodiment of FIG. 11E, the covering 98may cover a larger longitudinal portion of the underlying leads 44 andmay surround multiple leads, and thus may be referred to as “full.” Onceeach electrode 38 is anchored to the leads 44, the electrode assemblies32, 34 may be inserted into the lumens of catheter 10 and aligned withwindows 18, 16.

Electrodes Supported by Tubular Members

FIGS. 12A-12K illustrate yet another embodiment of electrode assemblies32, 34. In this embodiment, tubular members 100 may support the distalends 102 of leads 44 and hold the distal ends 102 adjacent to electrodes36, 38.

FIG. 12A illustrates a catheter 10; FIG. 12B illustrates a perspectiveview of a distal electrode assembly 34; FIG. 12C illustrates aperspective view of a proximal electrode assembly 32; FIG. 12Dillustrates a side view of the distal electrode assembly 34 of FIG. 12B;FIG. 12E illustrates a side view of the proximal electrode assembly 32of FIG. 12C; FIG. 12F illustrates a transverse cross-sectional view of adistal electrode 38 of FIG. 12D; FIG. 12G illustrates a transversecross-sectional view of a proximal electrode 36 of FIG. 12E; 12Hillustrates a transverse cross-sectional view of the catheter of FIG.12A with two distal electrode assemblies 34 of FIG. 12B within thecatheter lumens; FIG. 12I illustrates a transverse cross-sectional viewof the catheter 10 of FIG. 12A with two proximal electrode assemblies 32of FIG. 12C within the catheter lumens; FIG. 12J illustrates the view ofFIG. 12H with ECG wires through a central lumen of the catheter 10; andFIG. 12K illustrates the view of FIG. 12I with ECG wires through acentral lumen of catheter 10.

FIGS. 12B-12G illustrate the proximal and distal electrodes 36, 38 ofthe proximal and distal electrode assemblies 32, 34, respectively. Ascan be seen in the figures, electrode assemblies 32, 34 include leads44, similar to other embodiments. As shown most clearly in FIGS. 12F and12G, the distal portions 102 of leads 44 may include exposed conductivemembers 45 and may be attached by welding or any other method to theexterior of a tubular member 100 and to the interior of electrodes 36,38. The tubular member 100 may be 1-6 mm in length, 2-4 mm in length,and in one embodiment about 3 mm in length, although the tubular member100 may be any other suitable length. The tubular member 100 may be astainless steel hypodermic tube. (In FIGS. 12B-12E, tubular members 100are not shown and would be all or mostly covered by electrodes 36, 38.Distal portions 102 of leads 44 are labeled in FIGS. 12D and 12E to showtheir general location, although they are underneath electrodes 36, 38.)As can also be seen in FIGS. 12F and 12G, the distal portions 102 ofleads 44 may cause the electrodes 36, 38 to protrude radially outward.

Each lead 44 may travel proximally through any electrodes 38, 36 thatare positioned more proximally than the electrode to which the distalend 102 of that lead is attached. For example, referring to FIG. 12B,the lead 44 that is attached to the most distal electrode 38 of thedistal electrode assembly 34 may travel proximally through the other twoelectrodes 38 and through all six proximal electrodes 36. Referring toFIG. 12C, the lead 44 attached to the most distal electrode 36 maytravel proximally through each of the other five electrodes 36.

In one embodiment, the distal electrode assembly 34 may include threeleads 44—one for each electrode 38. Similarly, the proximal electrodeassembly 32 may include six leads 44—one for each electrode 36. As theleads 44 of each electrode assembly 32, 34 join together, the leads maybe coiled to form cables 48, 40. At more distal locations, cable 48(formed of leads 44 from distal electrode assembly 34), may include oneor two leads. At more proximal locations, such as proximal to the mostproximal electrode 38, cable 48 may include three leads 44. Similarly,at more distal locations, cable 40 (formed of leads from proximalelectrode assembly 32), may include one, two, three, four, or fiveleads. At more proximal locations, such as proximal to the most proximalelectrode 36, cable 40 may include six leads 44.

FIGS. 12H and 12I illustrate cross-sectional views with the electrodeassemblies 34, 32 within lumens of the catheter 10. Although the lumensof catheter 10 illustrated in FIGS. 12H and 12I may be shapeddifferently than in FIG. 2, the catheter 10 may still include lumens 20,22 configured to receive proximal electrode assemblies 32, lumens 24, 26configured to receive distal electrode assemblies 34, a lumen 28configured to receive a guidewire, and a lumen 30 configured to receivea steering mechanism or other structures. As can be seen in FIG. 12H,distal electrodes 38 may be aligned with distal windows 16. FIG. 12Iillustrates proximal electrodes 36 aligned with proximal windows 18. Theleads 44 from distal electrode assemblies 34 can be seen in thecross-sectional view of FIG. 12I because the leads 44 may travelproximally through lumens 24, 26.

FIGS. 12J and 12K are similar to the views shown in FIGS. 12H and 12I,except FIGS. 12J and 12K illustrate two electrocardiography (ECG)conductive members 104 within lumen 30. ECG conductive members 104 maybe coupled to one or more ECG electrodes 106 (see FIG. 12A and FIG. 14)located at a distal end of catheter 10, for sensing ECG signals of apatient.

One benefit of the embodiments of FIGS. 12A-12K is that each electrode36, 38 may be movable with respect to other electrodes 36, 38. Althoughthe electrodes 36, 38 are connected by leads 44, the leads 44 typicallyare flexible. Therefore, when placing electrode assemblies 32, 34 withincatheter 10 during manufacture of the medical device 50, this embodimentallows each electrode 36, 38 to be positioned within its respectivewindow 18, 16 at least partially independently of other electrodes.Independent positioning of the electrodes may allow positioning errorsto be minimized, as opposed to embodiments in which electrodes 36, 38are fixed to other electrodes by a catheter or other rigid structure.

Arcuate Electrodes

FIGS. 13A-13K illustrate an embodiment that is similar to the embodimentshown in FIGS. 12A-12K. Similar features from the embodiment of FIGS.12A-12K will not be repeated here. The main difference between theembodiment of FIGS. 13A-13K and the embodiment of FIGS. 12A-12K is thateach of the electrodes 36, 38 of FIGS. 13A-13K may form an arcuate shapethat functions to hold and contact the distal ends 102 (includingexposed conductive members 45) of leads 44. The proximal and distalassemblies 32, 34 of FIGS. 13A-13K may or may not include tubularmembers 100.

As shown in FIGS. 13F and 13G, each of the electrodes 36, 38 may beC-shaped and may have an outer wall 108 and an inner wall 110. The outerwall 108 and the inner wall 110 of an electrode may sandwich the exposedconductive member 45 at the distal end 102 of a lead 44.

Electrocardiography Electrodes

FIG. 14 illustrates two ECG electrodes 106 and their associatedcomponents. As with all other features in this application, the ECGelectrodes 106 may be used with any of the other embodiments describedherein. The ECG electrodes 106 may be located at a distal end of acatheter 10 (see FIG. 12A). In one embodiment, the catheter 10 mayinclude two ECG electrodes 106, although in some embodiments thecatheter 10 may include one electrode 106 or more than two electrodes106. A conductive member 104, which may be insulated, may connect eachelectrode 106 to an ECG system located outside of the patient, The ECGconductive members 104 may be braided or twisted together and may besurrounded by a non-conductive layer 105 (also shown in FIGS. 12J and12K).

The electrodes 106 may monitor a patient's heart rate. Heart ratemonitoring may be beneficial during use of medical device 50 to alert amedical practitioner to changes in the patient's heart rate. Changes inthe patient's heart rate may be caused by the medical device 50stimulating certain nerves or by unintentional stimulation of thepatient's heart. Heart rate monitoring also may be relied on to achievesteady recruitment of a nerve. For example, the catheter 10 may movewhen a patient's heart beats, causing fluctuations in nerve stimulation.If the patient's heart rate is known, the electrical potential createdbetween a pair of bipolar nerve-stimulating electrodes can be adjustedin real time to deliver a constant charge to the nerve.

Steering Mechanisms

A variety of steering mechanism may be included in a medical device 50to help control positioning of catheter windows 16, 18, and thuselectrodes 38, 36, within a blood vessel. A steering mechanism may belocated within a central lumen 30 of catheter 10 or within other lumensof the catheter 10. It may be beneficial to position at least someelectrodes 36, 38 in close proximity to each target nerve, as havingelectrodes situated close to the nerve can reduce the amount of currentshunted through the blood and thus may reduce the electrical currentneeded to activate the nerve.

Several factors may help position the proximal windows 18 in a desiredlocation within a blood vessel. For example, the typical subclavian veinpenetration angle and the shape and elasticity of catheter 10 maycombine to position the proximal windows 18 along a posterior wall ofthe subclavian vein, in close proximity to the left phrenic nerve, whichnormally descends dorsal to the left subclavian vein.

To ensure that the distal portion of the catheter 10, including windows16 and their associated electrodes 38, is positioned in a desiredlocation with respect to the right phrenic nerve, the medical device 50may include stiffening elements and steering mechanisms. In oneembodiment, the stiffening elements and steering mechanisms may helpposition the distal set of electrodes 38 against a lateral wall of thesuperior vena cava, close to the right phrenic nerve.

Turn Member Steering Mechanism

Referring to FIGS. 15A-15C, a steering mechanism 112 may include asingle pre-shaped elongated member 114, such as a wire or tube (i.e.stainless steel, nitinol, hypodermic tube, etc.) to steer the catheter10. The elongated member 114 may include a handle 120, a proximalportion 116 coupled to the handle 120, and a distal portion 118 that isbent with respect to the proximal portion 116. When the proximal portion116 is turned via the handle 120, the distal portion 118 maycorrespondingly turn into a variety of positions and may function toposition the distal end of catheter 10.

FIGS. 15A-15C illustrate the elongated member 114 in three differentpositions: a first position indicated by distal portion 118 a, a secondposition indicated by distal portion 118 b, and a third positionindicated by distal portion 118 c. FIG. 15A illustrates a front view ofthe steering mechanism 112 in three different positions, FIG. 15Billustrates a top view of steering mechanism 112 in three differentpositions, and FIG. 15C illustrates a view from the distal end of thesteering mechanism 112 to the proximal end of the steering mechanism 112when the steering mechanism 112 is in three different positions.

Elongated member 114 may be stiff enough to ensure that the distalportion of the catheter 10, which includes the distal electrodes 38, isplaced against the vessel wall. The elongated member 114 also may bestiff enough to transmit steering torque from the proximal handle 120 tothe distal portion 118.

Control Member Steering Mechanisms

Referring to FIGS. 16A-16E, another embodiment of steering mechanism 112may include one or more control members 122. In one embodiment, thecontrol members 122 may be pulled or pushed to bend or deflect a portionof catheter 10. The control members 122 may be surrounded by and mayslide longitudinally relative to one or more tubular members 124, suchas hypodermic tubes or compression coils. The tubular members 124 may beflexible. The steering mechanism 112 of this embodiment may furtherinclude a stiffening element 126, such as a tube or rod, which may beattached (e.g., by weld, adhesive, etc.) to the tubular members 124.

The embodiment of FIGS. 16A-16E may allow bidirectional steering ofcatheter 10. At a proximal end of the steering mechanism 112, a handle(not shown) may facilitate pulling or pushing of the control members 122relative to their corresponding tubular members 124. As shown in FIG.16C, the distal end of the steering assembly 112 may include gaps 128between tubular members 124. The gaps 128 may facilitate bending of thedistal end of the catheter 10. Once assembled, the steering mechanism112 may be adhered within the central lumen 30 or another lumen of thecatheter 10.

Referring to FIGS. 17A and 17B, in an additional or alternativeembodiment, tubular members 124 may include narrowed portions 130. Thenarrowed portions 130 may replace the gaps 128 or may be used incombination with gaps 128 to provide the desired flexibility. Thenarrowed portions 130 may be formed using a laser or by any othermethod.

Referring to FIGS. 18A-18E, in yet another embodiment of steeringmechanism 112, control members 122 may be located in separate lumens132, 134 within catheter 10. Similar to the embodiment of FIGS. 16A-16E,the control members 122 may be surrounded by one or more tubular members124, which may be hypodermic tubes or compression coils. In oneembodiment, each tubular member 124 does not surround a distal endportion of its respective control member 122. The distal end portion ofthe control member 122 may therefore be fixed to the distal end of itscorresponding lumen 132, 134. A distal end portion of each tubularmember 124 also may be fixed to its respective lumen 132, 134 at aposition more proximal than the fixed portion of the control member 122.A gap extending longitudinally along the lumen may be left between thefixed portion of the control member 122 and the fixed portion of itscorresponding tubular member 124 such that, when the control member 122is pulled or pushed relative to its tubular member 124, deflection ofthe catheter 10 occurs within the gapped space.

In yet another embodiment, referring to FIGS. 19A-19E, steeringmechanism 112 may include a single control member 122. The controlmember 122 may be surrounded by a tubular member 124 and may be pushedor pulled relative to the tubular member 124 to deflect the distal endof catheter 10. A distal portion of the control member 122 may be fixedwithin the distal end of lumen 30, or another lumen of catheter 10, andthe tubular member 124 may be fixed to a more proximal location withinlumen 30. Again, a gap may be formed between the fixed portion ofcontrol member 122 and the fixed portion of tubular member 124 tocontrol the deflection locations of the catheter 10. In one embodiment,the control member 122 may be pulled to deflect the catheter tip in onedirection and pushed to deflect the catheter tip in the other, oppositedirection.

In some embodiments, any of the steering mechanisms described above mayinclude a balloon, which may be inflated to assist in urging the distalportion of the catheter 10 and the distal electrodes 38 against thesuperior vena cava lateral wall. The balloon may be attached to a sideof the catheter opposite the windows corresponding to distal electrodes38. Upon inflation of the balloon, electrodes 38 may be urged towards awall of the superior vena cava.

Catheter Embodiments

Catheter Window Arrangements

Referring to FIGS. 20A-20C, the windows 16, 18 of catheter 10 may have avariety of alternative configurations. For example, instead of beingaligned as shown in FIG. 1, windows 16 may be offset from other windows16, and windows 18 may be offset from other windows 18 with respect to aproximal-distal line 136 on the exterior surface of catheter 10 or withrespect to a circumferential line 138 around the circumference ofcatheter 10. For example, windows 16 may be offset from each other ifthe more proximal window 16 does not lie on the same proximal-distalline 136 drawn through the center of the most distal window 16. Eachwindow 18 of FIGS. 20B and 20C may be offset from other windows 18 withrespect to circumferential lines 138 drawn through the center of windows18. Embodiments of catheter 10 include windows 16, 18 with anyconfiguration of offset and non-offset windows. As noted earlier, theset of windows 16 or rows of windows 16 may be offset from the set ofwindows 18 or rows of windows 18 with respect to a proximal-distal line136.

In addition to electrode proximity to the nerves, electrodeconfiguration relative to the nerve, as determined by windows 16, 18,may reduce the amount of electrical current required to stimulate nerveaxons. Nerve axons may require lower activation currents when theelectrodes and the direction of current flow are parallel to or alongthe nerve, thus producing a longitudinal transmembrane depolarization ofsufficient magnitude to initiate action potentials. The direction thenerve courses is not exactly known and can vary from one individual toanother.

Providing a plurality of different possible electrode configurationspermits selection of sets of electrodes to be used for nerve stimulationin an individual. Using proximal electrodes 36 as an example, electrodepairs may be arranged in a straight line (e.g., along circumferentialline 138 as in FIG. 20A), staggered (e.g., FIG. 20B), or angled (e.g.,FIG. 20 c) along a circumference of the catheter 10 to ensure that thenerves may be effectively stimulated. Referring to FIG. 20A, thecircumferential line 138 may pass through (or over) the center of twoelectrodes, or the circumferential line 138 may pass through (or over)other portions of the two electrodes (e.g., the pair of electrodes maybe slightly offset). Referring to FIG. 20B, staggered electrode pairsmay be arranged such that the longitudinal distance (along aproximal-distal line parallel to the longitudinal axis of catheter 10)between longitudinally adjacent electrodes (such as between electrodes18 a and 18 b), is approximately equal to the longitudinal distancesbetween other pairs of longitudinally adjacent electrodes, such as 18 band 18 c. Referring to FIG. 20C, angled pairs of electrodes may bearranged such that planes passing through the center of the pairs ofelectrodes do not form a right angle with respect to the longitudinalaxis of the catheter 10. Thus, the staggered electrode embodiment ofFIG. 20B is a subset of the angled electrode embodiment of FIG. 20C, andthe embodiment of FIG. 20A in which a circumferential line 138 passesthrough or over non-center portions of electrode pairs also may beconsidered to include angled electrode pairs. The electrodeconfiguration may be varied along the catheter 10 to account for theanatomical differences found among different patients. Selectingappropriate electrode pairs can provide effective nerve stimulationdespite these differences.

Pre-Shaped Catheter

FIG. 21 illustrates a medical device 50 having a pre-shaped catheter 10,with electrodes 36, 38 according to any embodiments disclosed herein.The pre-shaped catheter 10 may have arcuate, coiled, s-shaped, u-shaped,or any other pre-shaped portions. The pre-shaped catheter 10 may helpensure that the electrodes 36, 38 are in close contact with the vesselwall and thus closer to the phrenic nerve or other nerves, even inindividuals where the right phrenic nerve may course more anteriorly orposteriorly than normal.

The pre-shaping of the catheter 10 may be accomplished, for example, bya stiffening element inserted within the catheter lumens, or pre-shapedduring the manufacturing process. The pre-shaped catheter 10 may beflexible but may have some stiffness and may tend to return to itspre-shaped configuration. When inserted over a stiffer guidewire, thecatheter 10 may straighten for the ease of insertion. When the guidewireis taken out, the catheter 10 may return to its pre-shaped form.

Catheter with Elongated Openings

Referring to FIGS. 22A-24B, in additional or alternative embodiments,the catheter 10 may include elongated openings 140 along the itsexterior. The elongated openings 140 may connect the exterior of thecatheter 10 to an interior lumen and may be referred to as slits orchannels. As shown in FIGS. 22A-22B, the elongated openings 140 mayextend along the full length of the catheter 10. Additionally oralternatively, as shown in FIGS. 23A-23B, the elongated openings 140 mayextend along part of the length of the catheter 10. As shown in FIGS.24A and 24B, the elongated openings 140 may additionally oralternatively be covered by a sleeve 142.

Threading electrode assemblies 32, 34 through the lumens of catheter 10during assembly of medical device 50 may present challenges due to thelength of the lumens and their small diameter. In the embodiments ofFIGS. 22A-24B, the electrode assemblies 32, 34 may be inserted into oneor more lumens of catheter 10 through elongated openings 140. Theability to access the lumens of the catheter 10 from locations radiallyoutside of the lumens, rather than from the proximal and distal ends ofthe lumens, may simplify installation of electrical leads 44 and othercomponents of the medical device 50 during the manufacturing process.

The elongated openings 140 may be created during an initial extrusion ormolding process to form catheter 10 or may be created during a laterstep. Some non-limiting examples of suitable polymers for the firstextrusion or molding are: low and high-density thermoplasticpolyurethanes such as polyester, polyether, and polycarbonate-basedvarieties; polycarbonate-based polyurethanes; and polyamides (nylon) andpolyamide block copolymers (PEBA).

As shown in FIGS. 24A and 24B, after the electrode assemblies 32, 34 areinstalled in the lumens of catheter 10, an outer sleeve 142 may bethreaded over the catheter 10 to secure the wire assemblies within thelumens. The outer sleeve 142 may be a polymeric tubular sleeve and maybe formed by extrusion. The inner diameter of the outer sleeve 142 maybe large enough to slide over the outside of the catheter 10 but may besmall enough to retain the electrode assemblies 32, 34 within the lumensof the catheter 10 after it has been slid over the catheter 10. Theouter sleeve 142 may extend in a proximal-distal direction along adesired length of the catheter 10.

The outer sleeve 142 may be formed of a thin, thermoplastic materialsuch as, but not limited to, polyamide, polyether block amide,polyurethane, silicone rubber, nylon, polyethylene, fluorinatedhydrocarbon polymers, etc. Examples of polymer materials suitable foruse in the sleeve are commercially available under the trademarks PEBAX™and PELLETHANE™.

The outer sleeve 142 may be thermally bonded or otherwise mechanicallyattached to the catheter 10 by any of a number of methods. In one suchmethod, a tubular member, which may be formed by extrusion, may beplaced over and around both the catheter 10 and the outer sleeve 142.The tubular member may be shrinkable to compress against the outersleeve 142. For example, the tubular member may comprise heat shrinktubing. The heat shrink tubing can be formed of one or more layersdepending upon the desired properties. As an example, heat-shrink tubingfrom Parker TexLoc (Fort Worth, Tex.) has two layers for electricalinsulation. Texflour fluoropolymer double-shrink heat shrinkable tubinghas an outer layer of PTFE heat shrink with an inner layer of FEPtubing. When using double shrink tubing, the catheter 10 may beencapsulated by the FEP tubing as the PTFE shrinks, melting the FEP andcreating a waterproof protective covering which is desirable for avariety of applications including RF and electrical stimulation devices.

Thermal energy then may be applied to the heat shrink tubing to compressthe heat shrink tubing around the outer sleeve 142 and the catheter 10.Contraction of the heat shrink tubing provides a compressive forcedirected radially inward on the outer sleeve 142. The compressive forceexerted by the heat shrink tubing helps secure the outer sleeve 142 tothe catheter 10.

At the same time, or in a later step, thermal energy (e.g. RF heating,electromagnetic induction heating, etc.) may be applied to the assemblycomprising the heat shrink tubing, the outer sleeve 142, and thecatheter 10. The thermal energy may be sufficient to elevate thetemperature of the assembly in order to induce bonding of the outersleeve 142 to the catheter 10. The combination of the compressive forcegenerated by the heat shrink tubing and the thermal energy heating thematerials above their respective melt temperatures will serve to bondthe outer sleeve 142 and the catheter 10 together. The thermal energy istypically not high enough to create a bond between the heat shrinktubing and the polymeric sleeve nor is it high enough to damage theintegrity of the catheter assembly.

The heat shrink tubing may then be removed from the assembly comprisingthe catheter 10 (which is received inside the outer sleeve 142). A slit,notch, perforations, or other weakened regions may be used to assistwith the removal of the heat shrink tubing from the assembly. In somecases, the shrink tubing may be constructed of a biocompatible materialsuch as EPTFE and can be left on the catheter assembly.

Within lumens of catheter 10 according to any embodiments disclosedherein, it may be desirable to insert a support structure, such as apolytetrafluoroethylene (e.g., Teflon) coated mandrel, which may provideinterior support to maintain the structure of the catheter 10 andpreserve the patency of the longitudinal lumen throughout themanufacturing process. The support structure can later be removed bypulling it through either the distal or proximal openings in the lumen.In some cases the support structure can be stretched and elongated,thereby reducing its cross-sectional area, prior to removal.

One or more outer sleeves 142 of different materials, thicknesses, ormaterial properties (e.g. durometer) can be used at various locationsalong the length of catheter 10 to alter various physical properties(e.g. stiffness, torqueability, friction, etc.) at specific locationsalong the length of the finished catheter. For example, a flexiblesleeve 142 could be utilized at the distal portion of the catheter 10 toallow the tip of the catheter 10 to more easily track along a guidewire.A more rigid sleeve 142 could be used at the proximal portion of thecatheter 10 to allow for more pushability or torqueability when graspingthe distal end of the catheter 10. Adjacent sleeves 142 could bebutt-welded or otherwise coupled end-to-end during the final formingprocess. Lap-joints or scarf joints may optionally be used to form asmoother transition between adjacent sleeves 142.

Other elements or structures may be incorporated into the catheter 10construction using the assembly method described above. As one example,to help provide a desirable shape or contour to the distal end of thecatheter 10, a shaping element may be inserted into one of the elongatedopenings 140, or into an enclosed lumen, at a desired location along thefirst extrusion. The shaping element may be formable or pre-formed toimpart a desired configuration (e.g. a desired curvature) to thecatheter 10. The shaping element may be pre-formed or formed to causethe catheter 10 to curve in a plane having a desired angularrelationship, such as, for example, to aid in positioning electrodes 36,38 of the medical device 50.

The shaping element may be resiliently flexible. In some embodiments,the shaping element may comprise a predetermined length of e.g. nitinolwire, ribbon, spring, etc. In some embodiments, the shaping element maycomprise a temperature-dependent shape-memory material such as ashape-memory alloy. In some embodiments, the shaping element may beconstructed to assume a desired shape after the catheter 10 has enteredthe body of a patient. For example, body heat may cause a shape-memoryshaping element to change to a desired shaped configuration, or anexternal source of energy (e.g. an electrical current) may be applied tocause a shape change of a shaping element by a thermal or othermechanism. In some embodiments the shaping element becomes more curvedupon actuation.

Alternative Lead Embodiments

Referring to FIGS. 25A-26H, in an additional or alternative embodiment,one or all of the electrode leads 44 may be embedded in a flexibleribbon cable 144. The ribbon cable 144 may include multiple insulatedleads 44 connected along their lengths to form a single planarstructure. The planar structure may be flexible to form other shapes.Similar to other leads 44 described herein, the leads 44 of the ribboncable 144 may include an elongated conductive member 45 surrounded by alayer of non-conductive material 46, such as insulation.

In the embodiment of FIGS. 25A-25C, the ribbon cable 144 may be closedas a flexible cylinder (e.g., formed around a mandrel and theapproximated ribbon edges fixed with adhesive along the length). Thisdesign may allow any of the leads 44 to be deinsulated at a point alongthe catheter length and attached to an electrode 36, 38, such as, forexample, a flexible foil electrode or an electrode formed according toany of the embodiments described herein. Two proximal electrodes 36 ofthe ribbon cable embodiment may be seen in the cross-section of FIG. 25Cand will be described in greater detail below. The exterior elongatedtubular member of catheter 10 may be formed around the ribbon cable 144using the heat shrink method previously described to form a smoothelectrically-insulating wall. Individual electrodes 36, 38 may beexposed through windows 18, 16 formed in the catheter 10, similar toother embodiments.

An advantage of the embodiment of FIGS. 25A-25C is that a larger portionof the entire catheter 10 cross-section may be available for guide wireand/or fluid lumen(s). As shown in FIG. 25C, the ribbon cable 144 may besupported by a support catheter 146, which may include the lumensdescribed in connection with other embodiments or may include theguidewire lumen 28 and the delivery lumen 148 shown in FIG. 25C. Anotheradvantage of the embodiment of FIGS. 25A-25C is its simplicity and easeof fabrication.

FIGS. 26A-26H illustrate use of ribbon cable 144 in greater detail.Referring to FIG. 26B, proximal electrodes 36 may contact leads 44within ribbon cable 144. Referring to FIG. 26C, distal electrodes 38 maycontact different leads 44 within ribbon cable 144. The ribbon cable 144may be held temporarily in a cylindrical form with a weak adhesive (suchas an adhesive that dissolves in contact with blood, such as e.g.,sucrose). As shown in FIGS. 26D and 26E, a guide wire lumen 30 or otherlumens may be permanently attached to the ribbon cable 144 (for exampleusing a strong biocompatible adhesive). The ribbon cable 144 and anysupport catheter 146 may be wrapped in a thin electrically-insulatingcovering to form catheter 10 (for example by sliding the assembly into asleeve 142 and using the previously described heat-shrink method or thelike). A seam may be opened (e.g. using a knife or laser) directly overthe ribbon cable 144 seam to transition the ribbon cable 144 from theclosed position shown in FIG. 26D to the open position shown in FIG.26E. An adhesive may be used to transition the ribbon cable 144 from theposition shown in FIG. 26E to the position shown in FIG. 26D. As inother embodiments, windows 16, 18 may be formed in the exterior coveringof the catheter 10 to reveal electrodes 36, 38 at their desiredlocations.

A catheter 10 having a ribbon cable 144 may be introduced into a bloodvessel of the body of a subject in its closed configuration (see FIG.26D). Once inside the vessel, the adhesive may dissolve in a matter ofseveral minutes and the ribbon cable 144 may be free to deploy into anearly flat configuration, which may be its preferred state due to thenatural elasticity of the ribbon cable 144. Optionally, two controlmembers 150, such as Nitinol or other springy metal wires, or pullwires, may be embedded along the edges of the ribbon cable 144, andtheir natural elasticity and/or operation may contribute to the desiredopen configuration shown in FIG. 26E.

Referring to FIG. 26F, the natural elasticity of the ribbon cable 144and/or the control members 150 may contribute to urge the ribbon cable144 toward the vessel wall in such a way that the electrodes areproximate to the vessel wall in the vicinity of a target nerve, such asright phrenic nerve 58. With this design, one or more of the catheterelectrodes 36, 38 exposed through windows 18, 16 is likely to be in veryclose proximity to the target nerve and may afford highly selectiverecruitment of the nerve with very low current or charge delivery.Furthermore, this design provides effective insulation of the electrodes36, 38 from the blood in the vessel, thus minimizing current spread tounwanted regions and maximizing recruitment selectivity of the targetnerve.

FIG. 26G is an isometric view of a catheter 10 having a ribbon cable 144intended for deployment inside a vessel. In this embodiment, theproximal portion of the catheter 10 may have a near-circular, tubularcross-section in regions where the ribbon cable 144 is adhered withpermanent adhesive that will not dissolve in blood. In contrast, thedistal portions of the catheter 10 are shown in FIG. 26G to have openedinto the open ribbon cable configuration where the attachment of ribbonedges was temporary and the adhesive was dissolved once inside the bloodvessel lumen. It is further seen in FIG. 26G that the distal portion ofthe catheter having a ribbon cable 144 may naturally adopt a corkscrew(or “helical”) configuration, the dimensions of which are determined bythe properties of the control members 150 embedded along the ribboncable edges. One configuration may be a corkscrew section ofapproximately 20 mm diameter and approximately 30 mm length. Such aconfiguration may ensure that some of the distal wires are in closeproximity with, for example, the target right phrenic nerve 58 coursingon the outside of the superior vena cava 64 (not shown in FIG. 24G butshown in FIG. 21).

FIG. 26H illustrates a control member 152 that can be used to restrictthe total length of the distal coiled portion of the catheter 10 havinga ribbon cable 144. The control member 152 may be attached to a pointnear the distal end of the catheter 10 and may run freely through alumen inside the proximal portion of the catheter, crossing to outsidethe patient where the proximal end of the pull wire can be controlled bythe practitioner. By pulling on the control member 152, the catheter 10having a ribbon cable 144 may be controlled to open maximally inside theSVC, ensuring that the ribbon surface is completely deployed against thevessel wall.

Medical Device Having a Barometer

The medical device 50 may include barometric correction that allows thedevice 50 to operate at different altitudes, since a patient receivingelectrical stimulation phrenic-nerve pacing of the diaphragm may need tobreathe a constant oxygen supply, but the density of air declines withaltitude. The natural correction is for the patient to breathe moredeeply and/or more rapidly to compensate. The medical device 50 or thecatheter 10 may include a gauge (e.g. a barometer) that measuresatmospheric pressure in order to compensate for altitude changes. Highaltitude performance is especially valuable to the military, any otheragency transporting injured people (ski resorts, mountain climbers) andmore generally, any patient who requires pacing and needs to travel inan aircraft.

Medical Device Equipped with Electronic Chip

The medical device 50 or the catheter 10 may be equipped with anelectronic chip that stores information about the catheter 10 and/or itsusage. The chip may be, for example, provided in a hub of the catheter10. In one embodiment, when the catheter 10 is coupled to a controller,the controller may read the chip and send signals to the electrodes 36,38 only if the chip has the correct encryption and/or makes a correctresponse etc. The chip may store information such as one or a pluralityof the catheter serial number; size (length and/or diameter); lotnumber; batch number; date manufactured; electrode arrangement;electrode interconnection information (pin-outs for a connectorconnected to the electrodes by conductors in the catheter); etc. Thecontroller may accept algorithm upgrades that only apply to certainserial numbers or catheter types determined with reference to theinformation stored in the chip.

Other Alternative Embodiments and Interpretation of Terms

As noted earlier, any of the components and features of any of theembodiments disclosed herein may be combined and used in any logicalcombinations with any of the other components and features disclosedherein. However, for the sake of example, some ways in which thedescribed example embodiments may be varied include:

-   -   different numbers of electrodes;    -   different electrode configurations;    -   different electrode fixing (crimp, adhesive, microweld, etc.);    -   different electrode shape (round, oval, circular, rectangular,        etc.);    -   different electrode material;    -   different electrode surface areas;    -   different electrode spacing;    -   different number or shapes of lumens;    -   different window shape/dimensions;    -   different catheter profile (e.g., +/−9Fr);    -   different catheter length; and/or    -   different steering mechanism.

Unless the context clearly requires otherwise, throughout thedescription and the claims:

-   -   “comprise,” “comprising,” and the like are to be construed in an        inclusive sense, as opposed to an exclusive or exhaustive sense;        that is to say, in the sense of “including, but not limited to”;    -   “connected,” “coupled,” or any variant thereof, means any        connection or coupling, either direct or indirect, between two        or more elements; the coupling or connection between the        elements can be physical, logical, or a combination thereof;    -   “herein,” “above,” “below,” and words of similar import, when        used to describe this specification, shall refer to this        specification as a whole, and not to any particular portions of        this specification;    -   “or,” in reference to a list of two or more items, covers all of        the following interpretations of the word: any of the items in        the list, all of the items in the list, and any combination of        the items in the list; and    -   the singular forms “a,” “an,” and “the” also include the meaning        of any appropriate plural forms.

Words that indicate directions such as “vertical,” “transverse,”“horizontal,” “upward,” “downward,” “forward,” “backward,” “inward,”“outward,” “left,” “right,” “front,” “back,” “top,” “bottom,” “below,”“above,” “under,” and the like, used in this description and anyaccompanying claims (where present), depend on the specific orientationof the apparatus described and illustrated. The subject matter describedherein may assume various alternative orientations. Accordingly, thesedirectional terms are not strictly defined and should not be interpretednarrowly.

Specific examples of systems, methods and apparatus have been describedherein for purposes of illustration. These are only examples. Thetechnology provided herein can be applied to systems other than theexample systems described above. Many alterations, modifications,additions, omissions, and permutations are possible within the practiceof this invention. This invention includes variations on describedembodiments that would be apparent to the skilled addressee, includingvariations obtained by: replacing features, elements and/or acts withequivalent features, elements and/or acts; mixing and matching offeatures, elements and/or acts from different embodiments; combiningfeatures, elements and/or acts from embodiments as described herein withfeatures, elements and/or acts of other technology; and/or omittingcombining features, elements and/or acts from described embodiments.

It is therefore intended that the following appended claims and claimshereafter introduced are interpreted to include all such modifications,permutations, additions, omissions, and sub-combinations as mayreasonably be inferred. The scope of the claims should not be limited bythe preferred embodiments set forth in the examples, but should be giventhe broadest interpretation consistent with the description as a whole.

We claim:
 1. A catheter, comprising: an elongated tubular member havinga plurality of separate lumens extending along a length of the elongatedtubular member, the elongated tubular member including a first pluralityof apertures in an exterior wall of the elongated tubular member and asecond plurality of apertures in the exterior wall, wherein the secondplurality of apertures is located distal to the first plurality ofapertures; proximal electrodes located within the elongated tubularmember, wherein each of the proximal electrodes is positioned radiallyinward of a corresponding one of the first plurality of apertures, andwherein a first elongated electrode assembly positioned in a first lumenof the plurality of lumens supports a first plurality of the proximalelectrodes, and a second elongated electrode assembly positioned in asecond lumen of the plurality of lumens supports a second plurality ofthe proximal electrodes; and distal electrodes located within theelongated tubular member, wherein each of the distal electrodes ispositioned radially inward of a corresponding one of the secondplurality of apertures, and wherein a third elongated electrode assemblypositioned in a third lumen of the plurality of lumens supports a firstplurality of the distal electrodes, and a fourth elongated electrodeassembly positioned in a fourth lumen of the plurality of lumenssupports a second plurality of the distal electrodes.
 2. The catheter ofclaim 1, wherein the elongated tubular member is configured to beinserted into a venous system of a patient so that the proximalelectrodes are proximate a left phrenic nerve, and the distal electrodesare proximate a right phrenic nerve.
 3. The catheter of claim 1, whereinthe first elongated electrode assembly includes a first plurality ofelongated conductive members, wherein each electrode of the firstplurality of the proximal electrodes is electrically coupled to acorresponding one of the first plurality of elongated conductivemembers.
 4. The catheter of claim 3, wherein the second elongatedelectrode assembly includes a plurality of second elongated conductivemembers, wherein each electrode of the second plurality of the proximalelectrodes is electrically coupled to a corresponding one of the secondplurality of elongated conductive members.
 5. The catheter of claim 4,wherein the third elongated electrode assembly includes a plurality ofthird elongated conductive members, wherein each electrode of the firstplurality of the distal electrodes is electrically coupled to acorresponding one of the third plurality of elongated conductivemembers, and the fourth elongated electrode assembly includes aplurality of fourth elongated conductive members, wherein each electrodeof the second plurality of the distal electrodes is electrically coupledto a corresponding one of the fourth plurality of elongated conductivemembers.
 6. The catheter of claim 1, wherein the proximal electrodesinclude bipolar electrode pairs positionable to stimulate a left phrenicnerve, and the distal electrodes include bipolar electrode pairspositionable to stimulate a right phrenic nerve.
 7. The catheter ofclaim 1, wherein a pair of the proximal electrodes includes bipolarelectrodes configured to stimulate a first nerve, and a pair of thedistal electrodes includes bipolar electrodes configured to stimulate asecond nerve.
 8. The catheter of claim 1, wherein bipolar electrodepairs of the proximal electrodes are configured to be selectivelyactivated to create an electrical field extending radially outwards fromonly a portion of a circumference of a longitudinal section of thecatheter that includes the proximal electrodes, and bipolar electrodepairs of the distal electrodes are configured to be selectivelyactivated to create an electrical field extending radially outwards fromonly a portion of the circumference of a longitudinal section of thecatheter that includes the distal electrodes.
 9. The catheter of claim1, wherein electrodes supported by the first electrode assembly arealigned along a single longitudinal axis of the first lumen.
 10. Thecatheter of claim 1, wherein each of the proximal and distal electrodesis electrically coupled to a corresponding elongated conductive member.11. The catheter of claim 1, wherein at least one of the plurality ofseparate lumens is configured to receive at least one of a guidewire orfluid.